Inflammation, fibrosis and ectopic calcification are common pathologies observed in calcific aortic valve disease (CAVD). Ectopic calcification is particularly detrimental to the mechanical functions of the vasculature, and is the major cause of valve failure in patients with CAVD, as well as bioprosthetic valves. In CAVD, the major treatment for calcification is valve replacement therapy, which is associated with considerable morbidity and mortality, as well as a significant re- implantation rate. There is currently no drug or cell therapeutics that specifically target prevention and/or regression of calcification in CAVD Our preliminary data suggest that monocyte-derived inflammatory cells have the potential to regulate ectopic calcification in vivo similar to monocyte-derived osteoclasts that regulate and resorb mineral in bone. Our overall hypothesis is that calcifications accumulate in CAVD, in part, due to the absence and/or deficiency of key inflammatory cell functions and mediators, such as those found in osteoclasts that are designed to inhibit and/or regress mineral. By engineering cells to enhance these functions, we may prevent and even remove unwanted calcifications. (End of Abstract)